Growth and paracrine factors regulating follicular formation and cellular function

2000 ◽  
Vol 163 (1-2) ◽  
pp. 11-20 ◽  
Author(s):  
K.P McNatty ◽  
A.E Fidler ◽  
J.L Juengel ◽  
L.D Quirke ◽  
P.R Smith ◽  
...  
Keyword(s):  
Cellular Function ◽  
Paracrine Factors

scholarly journals Single-cell RNA sequencing of human fetal epicardium reveals novel markers and regulators of EMT

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T.J Streef ◽  
T Van Herwaarden ◽  
A.M Smits ◽  
M.J Goumans
Keyword(s):  
Cell Culture ◽  
Single Cell ◽  
Rna Sequencing ◽  
Public Institution ◽  
Funding Source ◽  
Injury Response ◽  
Post Injury ◽  
Paracrine Factors ◽  
Adult Heart ◽  
Single Cell Rna Sequencing

Abstract Background The heart is covered by the epicardium, consisting of epithelial cells and a mesenchymal layer. The epicardium has been shown to be essential during cardiac development by contributing cells through epithelial-to-mesenchymal transition (EMT) and the secretion of paracrine factors. In the adult, the epicardium conveys a cardioprotective response after myocardial infarction, albeit suboptimal compared to the epicardial contribution to heart development. Although the developing epicardium has been characterised in mice and zebrafish, knowledge on the human fetal epicardium derives mostly from cell culture models. Therefore, direct analysis of the human fetal epicardium is vital as it provides new insights into the cellular and biochemical interactions within the developing heart, which can potentially contribute to enhancing the post-injury response. Aim To study the human fetal epicardium using single-cell RNA sequencing (scRNA seq) in order to determine its cellular compositionThe data are further explored to e.g.identify regulators of epicardial EMT. Methods Epicardial layers were isolated from four fetal human hearts (14–15 weeks gestation, obtained under informed consent and according to local ethical approval). Tissue was digested, and single live cells were sorted into 384-wells plates and sequenced. Data analysis was performed using R-packages RaceID3 and StemID2. Findings were validated using qPCR and immunohistochemistry. Results Analysis of 2024 cells reveals a clear clustering of the epicardial epithelium and the mesenchymal population. Importantly, we found that “classical” markers, such as Wilms' Tumor 1 and T-box transcription factor 18, are not specific enough to reliably identify the epicardium, but our analysis has provided markers that do allow for robust identification of the epicardium. Additionally, we were able to identify epicardial subpopulations based on their expression profile, and we are currently investigating these using immunohistochemistry in human fetal and adult heart tissue sections. To establish the regulation of epicardial activation we are focussing on the process of EMT within our dataset using RaceID2. From our analysis, several regulators of epicardial EMT are proposed that will be followed up on in vitro. Conclusions We identify various novel markers of the fetal epithelial epicardium, as well as characterizing markers of the mesenchymal layer. We also identified novel factors involved in epicardial EMT, and these are currently being validated in our cell-culture model. These data can provide new insights into the post-injury response in the adult heart. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Dutch Heart Foundation

scholarly journals Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Paracrine Factors ◽  
Dual Treatment

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.

scholarly journals A modular tool to query and inducibly disrupt biomolecular condensates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen N. Hernández-Candia ◽  
Sarah Pearce ◽  
Chandra L. Tucker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cellular Function ◽  
Biological Role ◽  
Cellular Biology ◽  
Condensate Formation ◽  
Health And Disease ◽  
Lateral Sclerosis

AbstractDynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.

scholarly journals Intra-mitochondrial reaction for cancer cell imaging and anti-cancer therapy by aggregation-induced emission

RSC Advances ◽  
2020 ◽  
Vol 10 (71) ◽  
pp. 43383-43388
Author(s):  
Sangpil Kim ◽  
Juhee Kim ◽  
Batakrishna Jana ◽  
Ja-Hyoung Ryu
Keyword(s):  
Cancer Therapy ◽  
Cancer Cell ◽  
Chemical Reactions ◽  
Cell Imaging ◽  
Cellular Function ◽  
Aggregation Induced Emission ◽  
Cancer Cell Imaging ◽  
Anti Cancer

Controlled intracellular chemical reactions to regulate cellular function remain a challenge in biology mimetic systems.

scholarly journals Understanding MCL1: From Cellular Function and Regulation to Pharmacological Inhibition

FEBS Journal ◽  
2021 ◽  
Author(s):  
Mónica Sancho ◽  
Diego Leiva ◽  
Estefanía Lucendo ◽  
Mar Orzáez
Keyword(s):  
Cellular Function ◽  
Pharmacological Inhibition
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